Abstract
In the brain, prior sublethal ischemia (preconditioning, PC) is known to produce ischemic tolerance of neurons to subsequent lethal ischemia. However, this mechanism was not fully delineated. The present study aims at elucidating what alterations in the brain for neuronal ischemic tolerance were induced by PC treatment using neuron/astrocyte co-cultures. Previous studies have revealed that during ischemia, neurons were killed by the release of glutamate mainly by the reversed uptake of astrocytic glutamate transporter GLT-1. Recently, however, we have demonstrated that such glutamate release from astrocytes during PC treatment plays a critical role for the PC-induced neuronal ischemic tolerance. Unexpectedly, in this study, after PC insult, neurons failed to acquire tolerance to glutamate toxicity, but the rise of extracellular glutamate during ischemia was suppressed for the protection of neurons. The PC treatment transiently decreased the expression of astrocytic GLT-1. Previous studies have suggested that neuron-derived factors are involved in the up-regulation of the level of GLT-1 expression. This study suggested that these factors were decreased after the PC treatment. Here we show that neuron-glia signaling responsible for the PC-triggered down-regulation of astrocytic GLT-1 seems crucial to the development of the PC-induced ischemic tolerance of neurons. [Jpn J Physiol 55 Suppl:S233 (2005)]
